Studies on DNA replication were carried out in three areas --bacterial, plant cells and mammalian cells in culture. Mammalian Cells -- An in vitro system of DNA synthesis has been developed using isolated cell nuclei. The efficiency of synthesis appears to be about 1/10 of that observed in vivo. Studies of HGPRTase mutants have supported the hypothesis that leaky mutants are heterozygotes containing wild type alleles whose gene product is "spoiled" through negative interaction with the products of the mutant allele. The results of these studies are being applied to the isolation of new DNA replication mutants which are cold sensitive for the synthesis of DNA. Plant Cells - The soybean system has been adopted for studies of DNA replication and for mutant isolation. Our first paper describing this sytem is now in press. We have succeeded in isolating DNA from plant nuclei and have characterized it by autoradiography, alkaline sucrose velocity sedimentation and CsCl density centrifugation of Bu labeled DNA. The results demonstrate that this DNA is synthesized semi-conservatively as short, tandemly arranged replicons which join to become large molecular weight DNA. BIBLIOGRAPHIC REFERENCES: Characterization of the Replication of E. coli in The Absence of Protein Synthesis. T. Kogoma and K.G. Lark. J. Mol. Biol. (1975) 94, 243-256. Evidence for Defined Lengths of DNA Replication Units in 'Satellite' DNA from D. Ordii. T. Hori and K.G. Lark. Nature (1976) 259 504-505.